Engineering anisotropic human stem cell-derived three-dimensional cardiac tissue on-a-chip.

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Stem Cell Biology

Background:

• Cardiovascular diseases (CVDs) remain a leading global cause of mortality.
• Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) show promise for in vitro cardiac modeling, but their immaturity limits clinical relevance.
• Engineered cardiac tissues require improved maturation to accurately model native myocardium.

Purpose of the Study:

• To develop a microfluidic platform for 3D cardiac tissue modeling using hPSC-CMs.
• To enhance the maturation and physiological relevance of engineered cardiac tissues.
• To create a tool for cardiovascular disease modeling and therapeutic testing.

Main Methods:

• Development of a microfluidic platform with staggered microposts for surface topography.
• Co-culture of hPSC-CMs with cardiac fibroblasts within a biomimetic collagen hydrogel.
• Long-term culture and induction of anisotropic tissue architecture.

Main Results:

• Engineered cardiac tissues exhibited well-defined sarcomeric striations and synchronous contractions after two weeks.
• Upregulation of key cardiac maturation genes (HCN1, KCNQ1, CAV1.2, CAV3.1, PLN, RYR2) was observed.
• The platform successfully matured both animal and human stem cell-derived cardiac tissues.

Conclusions:

• The developed microfluidic platform enables long-term maturation of engineered cardiac tissues.
• This technology provides a physiologically relevant model for cardiovascular disease research.
• The platform offers a novel tool for therapeutic testing and patient-specific disease modeling.